In the fruit fly Drosophila melanogaster, the morphogenetic process of dorsal closure occurs midway through embryogenesis. During closure, lateral epidermal cells elongate along their dorsoventral axis and spread dorsally to cover the embryonic dorsal surface. Dorsal closure mutants die during embryogenesis and exhibit a distinctive cuticular phenotype-- a single large hole in the dorsal cuticle. Others and we have cloned many of the genes required for closure. Subsequent molecular studies of the cloned gene products have revealed that they can be separated into a least three classes. The Class I and II dorsal-open group gene products play signaling roles in closure (DJNK and Dpp, respectively); the Class III gene products play structural roles and include the cell adhesion and cytoskeletal proteins that drive closure. None of the Class III molecules appear to be either transcriptionally or post-transcriptionally regulated targets of signaling, thus [unreadable] a missing class of dorsal-open group genes has been revealed. In the current application, we propose to test the hypothesis that the products of two dorsal-open group genes (raw, which we have cloned, and mmy, which we propose to clone) function to limit DJNK signaling to leading edge epidermal cells during closure, perhaps as part of a complex composed of transcription factors and kinases. In addition, we propose to exploit high throughput and genome-wide screens to identify the transcriptionally regulated targets of the DJNK and Dpp signaling cascades during closure. We expect that the molecules we identify in these screens will correspond the "missing links" between the signals (Class I and II dorsal-open group genes) and the effectors (Class III dorsal-open group genes) of closure. Finally, we propose to explore the role of the amnioserosa in directing closure. In particular, we propose to clone and characterize a newly identified amnioserosal gene product that likely functions in closure, perhaps as an initiating signal of DJNK signaling and morphogenesis. In the long run, we expect our studies to reveal the cell biological processes that are important driving forces in dorsal closure, and more generally the driving forces of morphogenesis. [unreadable] [unreadable]